Cargando…

Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains

Autosomal dominant hearing loss (ADHL) manifests as an adult-onset disease or a progressive disease. MYO7A variants are associated with DFNA11, a subtype of ADHL. Here, we examined the role and genotype–phenotype correlation of MYO7A in ADHL. Enrolled families suspected of having post-lingual sensor...

Descripción completa

Detalles Bibliográficos
Autores principales: Joo, Sun Young, Na, Gina, Kim, Jung Ah, Yoo, Jee Eun, Kim, Da Hye, Kim, Se Jin, Jang, Seung Hyun, Yu, Seyoung, Kim, Hye-Youn, Choi, Jae Young, Gee, Heon Yung, Jung, Jinsei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9028242/
https://www.ncbi.nlm.nih.gov/pubmed/35453549
http://dx.doi.org/10.3390/biomedicines10040798
_version_ 1784691567546597376
author Joo, Sun Young
Na, Gina
Kim, Jung Ah
Yoo, Jee Eun
Kim, Da Hye
Kim, Se Jin
Jang, Seung Hyun
Yu, Seyoung
Kim, Hye-Youn
Choi, Jae Young
Gee, Heon Yung
Jung, Jinsei
author_facet Joo, Sun Young
Na, Gina
Kim, Jung Ah
Yoo, Jee Eun
Kim, Da Hye
Kim, Se Jin
Jang, Seung Hyun
Yu, Seyoung
Kim, Hye-Youn
Choi, Jae Young
Gee, Heon Yung
Jung, Jinsei
author_sort Joo, Sun Young
collection PubMed
description Autosomal dominant hearing loss (ADHL) manifests as an adult-onset disease or a progressive disease. MYO7A variants are associated with DFNA11, a subtype of ADHL. Here, we examined the role and genotype–phenotype correlation of MYO7A in ADHL. Enrolled families suspected of having post-lingual sensorineural hearing loss were selected for exome sequencing. Mutational alleles in MYO7A were identified according to ACMG guidelines. Segregation analysis was performed to examine whether pathogenic variants segregated with affected status of families. All identified pathogenic variants were evaluated for a phenotype–genotype correlation. MYO7A variants were detected in 4.7% of post-lingual families, and 12 of 14 families were multiplex. Five potentially pathogenic missense variants were identified. Fourteen variants causing autosomal dominant deafness were clustered in motor and MyTH4 domains of MYO7A protein. Missense variants in the motor domain caused late onset of hearing loss with ascending tendency. A severe audiological phenotype was apparent in individuals carrying tail domain variants. We report two new pathogenic variants responsible for DFNA11 in the Korean ADHL population. Dominant pathogenic variants of MYO7A occur frequently in motor and MyTH4 domains. Audiological differences among individuals correspond to specific domains which contain the variants. Therefore, appropriate rehabilitation is needed, particularly for patients with late-onset familial hearing loss.
format Online
Article
Text
id pubmed-9028242
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-90282422022-04-23 Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains Joo, Sun Young Na, Gina Kim, Jung Ah Yoo, Jee Eun Kim, Da Hye Kim, Se Jin Jang, Seung Hyun Yu, Seyoung Kim, Hye-Youn Choi, Jae Young Gee, Heon Yung Jung, Jinsei Biomedicines Article Autosomal dominant hearing loss (ADHL) manifests as an adult-onset disease or a progressive disease. MYO7A variants are associated with DFNA11, a subtype of ADHL. Here, we examined the role and genotype–phenotype correlation of MYO7A in ADHL. Enrolled families suspected of having post-lingual sensorineural hearing loss were selected for exome sequencing. Mutational alleles in MYO7A were identified according to ACMG guidelines. Segregation analysis was performed to examine whether pathogenic variants segregated with affected status of families. All identified pathogenic variants were evaluated for a phenotype–genotype correlation. MYO7A variants were detected in 4.7% of post-lingual families, and 12 of 14 families were multiplex. Five potentially pathogenic missense variants were identified. Fourteen variants causing autosomal dominant deafness were clustered in motor and MyTH4 domains of MYO7A protein. Missense variants in the motor domain caused late onset of hearing loss with ascending tendency. A severe audiological phenotype was apparent in individuals carrying tail domain variants. We report two new pathogenic variants responsible for DFNA11 in the Korean ADHL population. Dominant pathogenic variants of MYO7A occur frequently in motor and MyTH4 domains. Audiological differences among individuals correspond to specific domains which contain the variants. Therefore, appropriate rehabilitation is needed, particularly for patients with late-onset familial hearing loss. MDPI 2022-03-29 /pmc/articles/PMC9028242/ /pubmed/35453549 http://dx.doi.org/10.3390/biomedicines10040798 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Joo, Sun Young
Na, Gina
Kim, Jung Ah
Yoo, Jee Eun
Kim, Da Hye
Kim, Se Jin
Jang, Seung Hyun
Yu, Seyoung
Kim, Hye-Youn
Choi, Jae Young
Gee, Heon Yung
Jung, Jinsei
Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains
title Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains
title_full Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains
title_fullStr Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains
title_full_unstemmed Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains
title_short Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains
title_sort clinical heterogeneity associated with myo7a variants relies on affected domains
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9028242/
https://www.ncbi.nlm.nih.gov/pubmed/35453549
http://dx.doi.org/10.3390/biomedicines10040798
work_keys_str_mv AT joosunyoung clinicalheterogeneityassociatedwithmyo7avariantsreliesonaffecteddomains
AT nagina clinicalheterogeneityassociatedwithmyo7avariantsreliesonaffecteddomains
AT kimjungah clinicalheterogeneityassociatedwithmyo7avariantsreliesonaffecteddomains
AT yoojeeeun clinicalheterogeneityassociatedwithmyo7avariantsreliesonaffecteddomains
AT kimdahye clinicalheterogeneityassociatedwithmyo7avariantsreliesonaffecteddomains
AT kimsejin clinicalheterogeneityassociatedwithmyo7avariantsreliesonaffecteddomains
AT jangseunghyun clinicalheterogeneityassociatedwithmyo7avariantsreliesonaffecteddomains
AT yuseyoung clinicalheterogeneityassociatedwithmyo7avariantsreliesonaffecteddomains
AT kimhyeyoun clinicalheterogeneityassociatedwithmyo7avariantsreliesonaffecteddomains
AT choijaeyoung clinicalheterogeneityassociatedwithmyo7avariantsreliesonaffecteddomains
AT geeheonyung clinicalheterogeneityassociatedwithmyo7avariantsreliesonaffecteddomains
AT jungjinsei clinicalheterogeneityassociatedwithmyo7avariantsreliesonaffecteddomains